The proposed work seeks to characterize the changes in extracellular myocardial potassium induced by acute ischemia, the relationship of these changes to the various pharmacological interventions on these changes. To accomplish these goals, intact swine hearts have been instrumented with a flexible valinomycin miniprobe capable of providing the online determination of extracellular K and the simultaneous ventricular myocardial uni- or bi-polar electrograms. In addition, single ventricular and Purkinje fibers have been studied with microelectrode techniques to determine the influence of an increase in extracellular potassium on the parameters determining conduction velocity, and the interaction between changes in K and other metabolic changes known to occur as a result of acute ischemia. To date, these studies have shown the following: 1) Major inhomogeneities of K changes occur within the ischemic zone. 2) Changes in ventricular activation parallel the K changes but may not totally be explained by the change in K. 3) 30% reduction in the rate of rise of the action potential upstroke is required before conduction velocity slows in the single fiber exposed to an increased extracellular K, and 4) Purkinje fibers are more sensitive than ventricular fibers to the effects of the increase in K. In the forthcoming year, we intend to explore these changes in greater depth in the hope that by so doing we will gain greater insight into the factors underlying sudden cardiac death and the influence of therapeutic maneuvers on these factors.